A fundamental question has pestered genetic scientists for decades: Do identical twins have the same DNA? Until recently, scientists thought the answer was yes. That’s because so-called monozygotic twins form when one egg fertilized by one sperm becomes an embryo and divides in two. (Fraternal twins form from two different eggs fertilized by two different sperm.) Slight differences between identical twins — including physical characteristics, personality and health — have been mainly attributed to environmental factors or to chemical markers that attach to genes. These markers act like a dimmer switch on a light and influence how strongly genes turn on or off, according to the University of Miami Miller School of Health.
Now, new research published in the journal Nature Genetics offers more to the story. Of 381 pairs of identical twins studied and two sets of identical triplets, scientists found that 15% of them had a “substantial number of mutations” specific to one twin but not the other, the researchers write. Nearly 40 pairs had more than 100 genetic mutations while 38 pairs showed no mutations at all.
“One particularly surprising observation is that in many twin pairs, some mutations are carried by nearly all cells in one twin but completely absent in the other,” Ziyue Gao, an assistant professor of genetics at the University of Pennsylvania (who was not involved in the research), told staff writer Nicoletta Lanese of Live Science.
Building on previous research from members of this group and other scientific teams, this DNA discovery shakes up long-held views about identical twins. To the question, “Do identical twins have the same DNA?” the answer is shifting to no, and it will likely influence future studies that explore the role environmental factors play in disease and human development.
“This certainly places a new kind of burden on those who use identical twins to establish the separation between nature and nurture,” lead author on the study, Kári Stefánsson, CEO and founder of the Iceland-based genetics company deCODE, told Catherine Offord of The Scientist.
For his team’s research, Stefánsson leveraged the unique population of Iceland, which has been voluntarily participating in DNA studies for decades, according to Science. Because few ancestors account for a large portion of Icelanders compared with other countries, genetic variants are easier to find in genomic sequences. Secondly, people there have kept detailed genealogical records that, for some, go back to the 9th century. Stefánsson’s company deCODE manages the records at the website Islendingabok.is.
The researchers uncovered mutations that differed between monozygotic twins by taking advantage of what the scientists already knew about the earliest stages of human development. For instance, once fertilized, an egg becomes a zygote that replicates itself by dividing to create more copies of its cells. Sometimes, the enzyme tasked with copying the billions of genetic building blocks of DNA, called base pairs, makes mistakes. Cells have ways of correcting these mistakes, but errors — or mutations — do slip through. Minor ones do no harm and result in indiscernible changes, if any. Major ones can show up as observable differences, such as hair color, or as diseases.
Every person starts life this way, including monozygotic twins. The difference is that the zygote divides, eventually becoming two separate embryos. Twinning typically occurs between one and seven days after fertilization, but in rare cases, it can happen up to 13 days later. The longer it takes for the zygote to divide, the more abundant its accumulated cells.
To tease out the extent of genetic differences between twins, Stefánsson and his colleagues sequenced the DNA of 381 pairs of twins and two sets of triplets, as well as the DNA from their parents, spouses and children, according to Live Science. This allowed the scientists to pinpoint whether a mutation was handed down to a child. If it was, it meant it had occurred very early in development, before cells had differentiated into either germline cells (found in eggs and sperm) or somatic cells (found in non-reproductive cells). The researchers also analyzed mutations that twins shared but not uniformly across all cells. This phenomenon, known as mosaicism, suggests the pair may have split apart a little later.
With these clues in hand, the scientists were able to determine the number of mutations that separated monozygotic twins, their type and the timing of their occurrence. As Stefánsson told Live Science, the study does not conclude where in the genome a mutation occurred. But it offers a caution to avoid overestimating the influence of the environment when, in reality, a genetic mutation may be the source of a given disease or trait.
Nature Versus Nurture
The degree to which genetics plays a role in making humans human is controversial. Early notions that natural selection and heritable traits directed one’s path in life led to theories such as Social Darwinism, which arose in the late 19th century and promoted “survival of the fittest” theories for humans. It justified imperialism and racism and gave rise to pseudoscientific ideas such as eugenics, which rationalized sterilization and genocide. As Robert Plomin explained in a Scientific American article, by the early 20th century, theories around nurture arose from the field of psychology, suggesting that family life played a bigger role. Geneticists pushed back again sometime around the 1960s, and it’s been a polite tug-of-war ever since.
Enter twin studies. In an article for the Atlantic, Erika Hayaski introduces Nancy Segal, a psychologist at California State University, Fullerton, who is a fraternal twin and has studied twins her entire career. A fascinating case involves the “Jim twins” — Jim Springer and Jim Lewis — who became the subject of Segal’s book “Born Together — Reared Apart.” Both Jims were adopted by different families and raised in Ohio. They lived just 40 miles apart and did not meet until they were 39 years old — but it was like they had lived similar lives. Both were named James, got migraines, bit their nails, smoked Salem cigarettes, drove light blue Chevrolet cars, had a pet dog named “Toy,” married a woman named Linda, got divorced and then married a woman named Betty.
“The Jim twins inspired the Minnesota Twins Reared Apart study, which Segal also worked on from 1982 to 1992. This research once again showed surprising similarities in identical twins’ habits, interests, intelligence, and religion despite their separate upbringings,” wrote Hayaski.
Long-term studies of monozygotic twins allow scientists to explore the different ways that genetics and the environment influence human development. The thinking has been that, because identical twins come from the same egg and sperm, researchers can hold genetics as constant and delve into other explanations for behavior, health and appearance. It was believed that differences between them could have more to do with other factors such as diets, exercise, stress, relationships and where they live.
But the results of these studies are not so black and white. Over time, scientists have seen the lines between nature and nurture blur, and although debates continue, they are more nuanced. “A strict dichotomy between genes and environment is no longer relevant; they work in concert,” said Segal.